目的 探讨乙肝表面抗原(hepatitis B surface antigen, HBsAg)阳性心脏死亡器官捐献(donation after cardiac death, DCD)供肝的选择性使用方法及对肝移植预后的影响。方法 选择2011-03至2017-09解放军总医院第三医学中心(原武警总医院)实施的HBsAg阳性DCD供肝肝移植为研究对象,采用双向性队列研究。全部病例均获取术中零点肝活检标本,对生存期超过1年者进行二次肝穿行病理学检查。分析肝移植术后乙肝病毒状况、肝功生化指标、凝血功能及患者生存情况,对比手术前后肝组织纤维化及炎性变化,将供肝零点炎性和纤维化程度与患者术后生存状况进行相关分析。结果 肝移植受者术后1年、3年和5年生存率分别为86.8%、75.5%和62.3%。随访期内血清HBsAg全为阳性,但HBV-DNA均得到良好控制。术后1年时存活者肝功能状况良好。与零点肝组织相比,术后随访期肝穿组织炎性程度显著减轻(1.98±0.67 vs 1.65±0.79,P=0.02),而纤维化程度无显著变化(0.83±0.58 vs 0.68±0.61,P=0.31)。零点肝组织炎性程度与术后1年时肝功能状况无关而肝组织纤维化程度与术后1年时血清总胆红素(Total bilirubin, TBIL)、国际标准化比率(International Normalized Ratio, INR)和终末期肝病模型评分(Model for end-stage liver disease, MELD score)呈正相关,相关系数分别为0.56(P=0.04)、0.59(P=0.02)和0.68(P=0.01)。本组病例随访期内死亡20例,其中原发性肝无功3例,F2期者2例(2/12),F3期者1例(1/3),其余死亡原因分别为肿瘤复发11例,感染5例,消化道出血1例。结论 对于HBsAg阳性DCD供肝,零点肝组织病理学检查对于指导供肝的合理使用具有重要意义,F0期和F1期者可正常使用,F2期者选择性用于病情较轻的受者为宜,F3期者最好不用。通过科学选择供受体,并给予合理抗乙肝措施,能使供肝得到充分利用并获得良好预后。
Abstract
Objective To study the selective use of donor livers after cardiac death (DCD) with hepatitis B surface antigen (HBsAg) positive and its effect on the prognosis of liver transplantation.Methods With informed consent, liver transplantation recipients of HBsAg positive cardiac dead organs donated by our hospital were studied, where bidirectional cohort study was used. Intraoperative zero hepatic biopsy specimens were obtained from each of these cases, and the secondary hepatic biopsy was performed on patients with a lifespan of more than 1 year. The status of hepatitis B virus, liver function biochemical index, coagulation function and patient survival after liver transplantation were analyzed. Liver fibrosis and inflammation changes before and after surgery were compared.Results The 1-year, 3-year and 5-year survival rates of liver transplant recipients were 86.8%, 75.5% and 62.3% respectively. Serum HBsAg of each patient was positive during the follow-up, but HBV-DNA was well controlled. the liver function of the survivors was good at 1 year after operation. The degree of inflammation of the liver perforating tissue was significantly reduced during postoperative follow-up (1.98±0.67 vs 1.65±0.79, P=0.02), while the degree of fibrosis was not significantly changed (0.83±0.58 vs 0.68±0.61, P=0.31). The degree of zero-point liver tissue inflammation was not related to the liver function at 1 year after surgery, while the degree of liver tissue fibrosis was positively correlated with total bilirubin (TBIL), International Normalized Ratio (INR) and Model for End-Stage Liver Disease (MELD score) at 1 year after surgery. The correlation coefficients were 0.56 (P=0.04), 0.59 (P=0.02) and 0.68 (P=0.01), respectively. In this study, 20 patients died during the follow-up, including 3 patients with primary hepatic reactive power, 2 patients with F2 stage (2/12), 1 patient with F3 stage (1/3), 11 patients with tumor recurrence, 5 patients with infection and 1 patient with gastrointestinal hemorrhage.Conclusions For HBsAg positive DCD donor livers, zero hepatic histopathological examination is of great significance in guiding the rational use of donor livers, F0 stage and F1 stage can be used normally, F2 stage is suitable for patients with mild disease, and F3 stage should not be used. With careful selection of donor receptors and proper anti-hepatitis measures, donor livers can be fully utilized and good prognosis can be obtained.
关键词
肝移植 /
HBsAg 阳性供肝 /
选择性使用 /
预后
Key words
liver transplantation /
HBsAg positive donor /
selective use /
prognosis
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基金
国家自然科学基金(81450066),原武警总医院课题(WZ20130203;WZ2014016),国家重大科学研究计划课题(2014CBA02001)。
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